The Radiation Biology and Oncology (RBO) program focuses on investigating the basic underlying molecular mechanisms of tumor radioresistance and normal tissue responses to radiation and how to optimally deliver radiation to improve the treatment of cancer. The RBO program has 18 members from 6 departments in the School of Medicine and School of Engineering. The RBO program has a funding base of more than $3.2 million in annual direct costs, of which more than $2.5 million is from the NIH and other peer-reviewed funding sources. More than $1.8 million is awarded by the NCI. The major objectives of the RBO program are to conduct research in molecular radiobiology and medical physics leading to clinical trials in radiation oncology; to provide a research environment conducive to extensive scientific collaborations; and to develop novel approaches for improving radiation therapy. Important topics of basic research include growth factor and inflammatory responses, DNA damage and repair, and novel radiologic imaging techniques, which lead to development of unique approaches to improving the efficacy of radiation therapy. Ongoing translational studies explore the use of novel small molecules or clinically available agents that work through targeting pathways identified as important in radiation responses. In addition, the medical physics research program is closely integrated with both the molecular radiobiology and the clinical research programs, with the goal of improving targeting accuracy and delivery of radiation therapy. The combined efforts and integration of biology, physics and clinical research are working to achieve improved tumor control with decreased risk of complications. Clinical research is a major focus of the program. Since the last CCSG review, accrual to RBO investigator-initiated therapeutic Cancer Center trials has increased by 81% and enrollment onto investigator-initiated therapeutic trials represents 78% of total RBO therapeutic accruals. The research from the RBO program has produced 142 publications of which 18% represent intra-programmatic collaborations, 22% represent inter-programmatic collaborations, and 1 % represent both intra and inter programmatic collaborations. Thus, almost half of all papers published are from collaborations. RBO fosters the development of new research interactions by also organizing seminars and regular meetings, as well as focused discussion groups that have led to a steady increase in our collaborative projects and funding.